Objective:To evaluate the curative effects of 3D printed microporous titanium (tantalum) prosthesis in reconstruction of large segmental bone defects caused by lower extremity osteomyelitis.Methods:A retrospective study was conducted to analyze the clinical data of 18 patients who had been treated for large segmental bone defects caused by lower extremity osteomyelitis between January 2020 to May 2022 at Department of Orthopaedics, The 920th Hospital of Joint Logistics Support Force. There were 10 males and 8 females with an age of (45.3±14.1) years. The defects were at the left side in 13 cases and at the right side in 5 cases, at the femur in 11 cases and at the tibia in 7 cases. The duration of osteomyelitis was 1.0 (1.0, 3.5) years. The length of bone defects was 8.35 (6.50, 9.84) cm. Their bone defects were repaired by an individually 3D printed microporous titanium (tantalum) prosthesis after operative removal of osteomyelitis lesions. The wound healing was observed after surgery. The clinical efficacy was comprehensively evaluated by the Paley grading for bone defect healing, visual analog scale (VAS), lower extremity functional scale (LEFS), and imaging examination.Results:The postoperative follow-up period for the 18 patients was (12.2±0.3) months. Wound infection occurred 2 months after surgery in one patient who was treated with Ilizarov bone transfer after removal of the microporous titanium prosthesis. The remaining 17 patients had good postoperative wound healing. At the last follow-up, the 18 patients had a VAS pain score of 2.0(1.0, 4.0) points, significantly lower than the preoperative one [(6.1±2.3) points], and a LEFS score of 54.00(34.50, 69.25) points, significantly higher than the preoperative one [18.50(9.00, 26.50) points] ( P<0.05). At the last follow-up, according to the Paley grading, the bone union was rated as excellent in 16 patients, as good in 1 patient and as poor in 1 patient. The integration of femoral fractures with 3D printed microporous titanium prostheses was fine. Conclusion:In reconstruction of large segmental bone defects caused by lower extremity osteomyelitis, implantation of a 3D printed microporous titanium (tantalum) prosthesis is feasible and effective, not only reducing pain but also restoring the limb function.

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

Objective:To investigate the efficiency of biochemical screening and hotspot gene screening in the detection of neonatal inherited metabolic diseases.Methods:This was a prospective multi-center study.The study was carried out on 21 442 neonatal samples collected from 12 hospitals in 10 provinces from November 2020 to November 2021.The results of biochemical screening and hotspot gene screening were analyzed jointly.Biochemical screening methods included glucose-6-phosphate dehydrogenase deficiency enzyme activity assay and neonatal tandem mass spectrometry.Genetic screening analysis involved 135 genes associated with 75 neonatal diseases.Results:Of all the 21 442 neonates enrolled in the study, 21 205 were subject to biochemical screening.A total of 813 cases were positive in the initial screening, and 0.45% of them (95 cases) were diagnosed after recall.All the 21 442 neonates underwent gene screening.About 168 positive cases were detected in the initial screening, and 0.73% (156 cases) of them were confirmed finally.Biochemical and genetic screening improved the detection sensitivity of such diseases as primary carnitine deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, and 2-methylbutyrylglycinemia.Moreover, biochemical and genetic screening enabled the detection of more diseases, including the common single-gene genetic diseases such as thalassemia and Wilson disease.Conclusions:In neonatal screening, the combination of biochemical screening and gene screening expands the number of diseases detected and improve screening efficiency.

Objective:To investigate the incidence, clinical characteristics and prognosis of ornithine transcarbamylase deficiency(OCTD) in newborns in Zhejiang Province.Methods:A retrospective research was conducted.A total of 4 261 036 newborns from Department of Genetics and Metabolism, Children′s Hospital, Zhejiang University School of Medicine, between January 2009 and December 2021 were screened for inherited metabolic disorders using tandem mass spectrometry.OCTD was confirmed by urine organic acid and OTC gene analysis.Patients with OTCD received guidance on diet and lifestyle management, and were treated with citrulline and arginine.Long-term follow-up was performed.Their growth and intellectual development were evaluated. Results:A total of 7 patients with OCTD were diagnosed, with an incidence of 1.6/1 million.All patients were males.Two patients had neonatal-onset OCTD, and the other 5 had late-onset OCTD.Symptoms occurred several times in 6 patients, inducing hyperammonemia and hepatic impairment.One patient had no clinical manifestation.One patient died in the neonatal period.Blood citrulline levels were decreased in 7 patients to varying degrees.Uracil levels were increased in 4 patients, and 1 of them was complicated with elevated orotic acid levels.All patients had hemizygote variations in the OTC gene, including 6 missense variations(c.604C>T, c.386G>A, c.779T>C, c.1019C>T, c.594C>G, c.931G>A) and 1 intron variation(c.514-35C>G). Two variants(c.594C>G, c.514-35C>G) were never reported previously. Conclusions:The OTCD incidence by newborn screening is low with 1.6/1 million in Zhejiang province.All patients are males and present hypocitrullinemia.The clinical manifestations of OTCD are highly heterogeneous.The neonatal-onset form is severe and survivors always suffer serious sequelae.The late-onset form is mostly manifested with hyperammonemia and hepatic impairment.There may be association between phenotype and genotype.Two novel OTC variants are identified, which further expands the mutational spectrum.

OBJECTIVE: To investigate the genetic characterization of 3-hydroxyisovalerylcarnitine (C5-OH) metabolic abnormality in neonates. METHODS: Fifty two newborns with increased C5-OH, C5-OH/C3 and C5-OH/C8 detected by tandem mass spectrometry during neonatal screening were enrolled in the study. Genomic DNA was extracted from the whole blood samples of 52 cases and their parents. Seventy-nine genes associated with genetic and metabolic diseases including , were targeted by liquid capture technique. Variation information of these genes was examined by high-throughput sequencing and bioinformatic analysis, and then was classified based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The genetic types were classified as wild-type, -maternal-mutation, -paternal-mutation and -mutation. Wilcoxon rank-sum test was performed for the increased multiples of C5-OH calculated in neonatal screening. RESULTS: Twenty one variants (14 novel) were identified in 37 cases, 6 variants (5 novel) in 4 cases. The increased multiple of C5-OH calculated in -maternal-mutation and -mutation groups were significantly higher than that in wild-type group (all <0.05), while there was no significant difference between MCCC1-paternal-mutation group and wild-type group (>0.05). CONCLUSIONS Mutations on and genes are the major genetic causes for the increased C5-OH in neonates, and maternal single heterozygous mutation can contribute to the moderately to severely increased C5-OH.
Carbon-Carbon Ligases ; genetics ; Carnitine ; analogs & derivatives ; metabolism ; Female ; Genetic Testing ; Genetic Variation ; Humans ; Infant, Newborn ; Male ; Mutation ; Neonatal Screening ; Urea Cycle Disorders, Inborn ; genetics

OBJECTIVETo screen fatty acid oxidation disorders (FAOD) in newborns in Zhejiang province.

METHODSA total of 1 861 262 newborns were screened for FAOD in Neonatal Screening Center of Zhejiang Province during January 2009 and December 2016. The blood samples from newborns were screened by tandem mass spectrometry, and diagnosis of FAOD was confirmed by urine organic acid measurement combined with genetic analysis. The prognosis and follow-up of patients with FAOD were also evaluated.

RESULTSOf 1 861 262 newborns screened, 121 cases of FAOD were diagnosed. Among 121 cases of FAOD, primary carnitine deficiency (PCD) was the most common type (=78, 64.5%), which was followed by short-chain acyl-CoA dehydrogenase deficiency (SCADD,=27, 22.3%), medium-chain acyl-CoA dehydrogenase deficiency (=5, 4.1%), multiple acyl-CoA dehydrogenase deficiency (MADD,=4, 3.3%), very long-chain acyl-CoA dehydrogenase deficiency (=3, 2.5%), carnitine palmitoyltransferase Ⅰ deficiency(=2, 1.7%)and carnitine palmitoyltransferase Ⅱ deficiency (CPTⅡD,=2, 1.7%). During 2-82 month follow-up, 15 patients were lost, 4 were dead (1 PCD, 1 MADD, and 2 CPTⅡD), and the remaining 102 subjects had normal intelligence and physical development without any clinical symptoms.

CONCLUSIONSPCD and SCADD are the most common FAODs in newborns in Zhejiang province. Most of FAOD patients are asymptomatic, and have normal growth and development after early intervention and management.

OBJECTIVETo analyze the results and follow up data of screening for newborn organic aciduria in Zhejiang province.

METHODSThe results and follow-up data of 1 861 262 newborns from Zhejiang province undergoing screening for organic aciduria during January 2009 and December 2016 were retrospectively analyzed. The acylcarnitine spectrum in urine samples was detected by tandem mass spectrum (MS/MS) and the positive patients were confirmed by urine gas chromatography mass spectrometry and/or gene analysis.

RESULTSNinety two cases of organic aciduria were confirmed with a prevalence of 1:20 200. Among 40 cases of methylmalonic academia (MMA), 13 (32.5%) were of MMA simple type and 27 (67.5%) were combined type. Genetic analysis showed 6 cases of MUT type and 1 case of CblB type out of 7 patients with MMA simple type, 10 cases of CblC and 1 case of CblF out of 11 patients with combined type, respectively. Six patients had propionic academia with a prevalence of 1:310 200, 7 had isovaleric academia (1:265 900), 6 had glutaric academia type 1 (1:310 200), 27 had 3-methylcrotonyl-CoA carboxylase deficiency (MCC, 1:68 900), 1 had 3-hydroxy-3-methylglutaric aciduria (1:1 861 300), 2 had β-ketothiolase deficiency (1:960 600), and 3 had biotinidase deficiency/holocarboxylase synthetase deficiency (1:620 400). Thirty-one patients had a disease onset at neonatal period, and 15 at post-neonatal period. Thirty-three patients had brain involvements or cranial imaging disorders. Three patients with MMA had kidney diseases or heomlytic uremic syndrome, and 3 had myocardial impairments. Twenty patients died during the follow-up.

CONCLUSIONSMMA is the most common newborn organic aciduria in Zhejiang province. Except MCC, most organic aciduria may lead to metabolism decompensation, complications or even death.

OBJECTIVETo analyze the result and follow-up data of screening for newborn amino acid metabolic disorders in Zhejiang province.

METHODSA total of 1 861 262 newborns were screened for amino acid metabolic disorders during January 2009 and December 2016 in Zhejiang province. The screening results and the follow-up data were analyzed retrospectively.

RESULTSOne hundred and sixty four cases were diagnosed as amino acid metabolic disorders with a prevalence of 1:11 349, including 83 with hyperphenylalaninaemia (1:22 400), 29 with neonatal intrahepatic cholestasis caused by citrin deficiency (1:64 138), 16 with methionine S-adenosyltransferase deficiency (1:116 250), 9 with maple syrup urine disease (1:206 667), 8 with argininemia (1:232 500), 7 with citrullinemia type Ⅰ (1:265 700), 6 with hyperprolinemia type Ⅰ (1:310 000), and 2 with carbamylphosphate synthetase Ⅰ deficiency(1:930 000). In addition, ornithine transcarbamylase deficiency, cystathionine β-synthase deficiency, argininosucoinate aciduria and tyrosinemia type Ⅰ were detected in one patient for each, respectively. Two patients had developmental delay, 7 patients were dead, and 2 cases of maple syrup urine disease were lost to follow-up.

CONCLUSIONSHyperphenylalaninaemia is the most common amino acid metabolic disease in newborns in Zhejiang province. Patients with amino acid metabolic disorders identified in newborn screening program can have chance for normal growth development by intervention.

Objective To explore the effects of isoflurane on blood plasma metabolites (BPM) and its correlation with cognitive dysfunction.Methods Thirty female Sprague-Dawley (SD) rats were randomly divided into two groups:rats in the control group (n =10) received 80％ oxygen for 2 hours (h);and rats in the isoflurane-treated group (n =20) were anesthetized with isoflurane and 80％ oxygen for 2 h.Cognitive functions were examined using a Y-maze test to explore the learning times of rats.The level of blood plasma metabolites was detected through gas chromatography-mass spectrometry (GCMS).Results The learning times of rats in the isoflurane-treated group was more than the learning times of rats in the control group [(70.75 ± 15.30) vs (45.40 ± 11.21),P ＜ 0.05].D-fructose,arabinofuranose,n-butylamine,and inositol significantly increased (P ＜ 0.05),respectively.Whereas,L-analine and L-proline significantly decreased (P ＜ 0.05) in isoflurane-treated rats when compared to those in the control rats (P ＜ 0.05).Moreover,plasma concentrations of d-fructose,arabinofuranose,n-butylamine,inositol,and L-proline were positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats.Conclusions Changes of plasma concentrations of inositol,and d-fructose in aged rats are useful in predicting the occurrence and progression of post-anesthesia cognitive dysfunction.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Death, Sudden ; etiology ; Hereditary Central Nervous System Demyelinating Diseases ; diagnosis ; etiology ; Humans ; Hydroxymethylglutaryl-CoA Synthase ; deficiency ; Infant, Newborn ; Male ; Mutation ; Oxo-Acid-Lyases ; genetics ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry